receptor-type tyrosine-protein phosphatase epsilon; protein-tyrosine phosphatase epsilon; R-PTP-epsilon (PTPRE)

Function

• isoform 1
  • involved in signal transduction pathways & phosphoprotein network topology in erythrocytes
  • may play a role in osteoclast formation & function
• isoform 2
  • acts as a negative regulator of insulin receptor signaling in skeletal muscle
  • regulates insulin-induced tyrosine phosphorylation of insulin receptor & insulin receptor substrate 1 (IRS-1), phosphorylation of protein kinase B & glycogen synthase kinase-3 & insulin induced stimulation of glucose uptake (putative)
  • interacts with GRB2 (putative)
  • homodimer; can form oligomers
  • dimerization is increased by oxidative stress & decreased by EGFR.
• isoform 1 & isoform 2
  • act as a negative regulator of FceRI-mediated signal transduction leading to cytokine production & degranulation, most likely by acting at the level of SYK to affect downstream events such as phosphorylation of SLP76 & LAT & mobilization of Ca+2 (putative)
  • phosphorylated on Tyr by tyrosine kinase neu
• a catalytically active cytoplasmic form (p65) is produced by proteolytic cleavage of either isoform 1, isoform 2 or isoform 3

protein tyrosine phosphate + H2O = protein tyrosine + phosphate

Structure

• isoform 1: glycosylated, monomer
• the tyrosine-protein phosphatase 2 domain (D2) mediates dimerization
• the extreme N-terminal & C-terminal of the D2 domain act to inhibit dimerization & removal of these sequences increases dimerization & inhibits enzyme activity (putative)
• belongs to the protein-tyrosine phosphatase family receptor class 4 subfamily
• contains 2 tyrosine-protein phosphatase domains

Compartment

• isoform 1: cell membrane; single-pass type 1 membrane protein
• isoform 2:
  • cytoplasm, predominantly cytoplasmic
  • a small fraction is also associated with nucleus & membrane
  • insulin induces translocation to the membrane
• isoform 3: cytoplasm

Alternative initiation

• alternative promoter usage
• named isoforms=3

Expression

• expressed in giant cell tumor (osteoclastoma rich in multinucleated osteoclastic cells)
• up-regulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) in HL-60 cells

More general terms

• tyrosine phosphatase, receptor type
• plasma membrane protein
• glycoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5791
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5791
• OMIM: https://mirror.omim.org/entry/600926
• UniProt: http://www.uniprot.org/uniprot/P23469.html